Photo by Petr Kratochvil

Childhood acute lymphoblastic leukemia (ALL) may be preventable, according to a researcher.

Mel Greaves, PhD, of The Institute of Cancer Research in London, UK, reviewed more than 30 years of research and concluded that ALL develops in 2 steps—genetic mutation before birth and further genetic change after birth triggered by infection.

The evidence suggests that infection early in life is beneficial to prime the immune system, but later infection without earlier priming can trigger ALL.

So priming the immune system in the first year of life could potentially prevent childhood ALL, according to Dr Greaves.

He outlined this theory in Nature Reviews Cancer.

Dr Greaves compiled more than 30 years of research into genetics, cell biology, immunology, epidemiology, and animal modelling of ALL.

The evidence led him to conclude that ALL begins with a genetic mutation that occurs before birth and predisposes a child to leukemia.

The disease is triggered later, in childhood, by exposure to one or more common infections. This primarily occurs in children who experienced “clean” childhoods in their first year of life, without much interaction with other infants or older children.

Dr Greaves challenged previous reports of possible environmental causes for ALL, such as ionizing radiation, electromagnetic waves, or man-made chemicals. He argued that none of these reports are supported by robust evidence.

Instead, he believes there is strong evidence suggesting that infection later in childhood, in the absence of earlier priming, can trigger ALL.

Dr Greaves’ studies of identical twins with ALL showed that 2 mutations were required for ALL development. The first arises in one twin in the womb but produces a population of pre-malignant cells that spread to the other twin via their shared blood supply. The second mutation arises after birth and is different in the twins.

Population studies and animal experiments suggest this second genetic hit can be triggered by infection, probably by a range of common viruses and bacteria. In one unique cluster of cases investigated by Dr Greaves and his colleagues, all cases were infected with flu virus.

In other work, researchers engineered mice with an active leukemia-initiating gene. When the team moved the mice from an ultra-clean, germ-free environment to one that had common microbes, the mice developed ALL.

Population studies have indicated that early exposure to infection in infancy, such as via day care attendance and breast feeding, can protect against ALL, probably by priming the immune system. This suggests childhood ALL may be preventable.

Dr Greaves is now investigating whether earlier exposure to harmless microbes could prevent leukemia in mice.

“I have spent more than 40 years researching childhood leukemia, and, over that time, there has been huge progress in our understanding of its biology and its treatment . . . ,” Dr Greaves said. “But it has always struck me that something big was missing, a gap in our knowledge [that failed to explain] why or how otherwise healthy children develop leukemia and whether this cancer is preventable.”

“This body of research is a culmination of decades of work and at last provides a credible explanation for how the major type of childhood leukemia develops. The research strongly suggests that ALL has a clear biological cause and is triggered by a variety of infections in predisposed children whose immune systems have not been properly primed. It also busts some persistent myths about the causes of leukemia, such as the damaging but unsubstantiated claims that the disease is commonly caused by exposure to electro-magnetic waves or pollution.”

“I hope this research will have a real impact on the lives of children. The most important implication is that most cases of childhood leukemia are likely to be preventable. It might be done in the same way that is currently under consideration for autoimmune disease or allergies, perhaps with simple and safe interventions to expose infants to a variety of common and harmless ‘bugs.’”

Photo by Petr Kratochvil

Childhood acute lymphoblastic leukemia (ALL) may be preventable, according to a researcher.

Mel Greaves, PhD, of The Institute of Cancer Research in London, UK, reviewed more than 30 years of research and concluded that ALL develops in 2 steps—genetic mutation before birth and further genetic change after birth triggered by infection.

The evidence suggests that infection early in life is beneficial to prime the immune system, but later infection without earlier priming can trigger ALL.

So priming the immune system in the first year of life could potentially prevent childhood ALL, according to Dr Greaves.

He outlined this theory in Nature Reviews Cancer.

Dr Greaves compiled more than 30 years of research into genetics, cell biology, immunology, epidemiology, and animal modelling of ALL.

The evidence led him to conclude that ALL begins with a genetic mutation that occurs before birth and predisposes a child to leukemia.

The disease is triggered later, in childhood, by exposure to one or more common infections. This primarily occurs in children who experienced “clean” childhoods in their first year of life, without much interaction with other infants or older children.

Dr Greaves challenged previous reports of possible environmental causes for ALL, such as ionizing radiation, electromagnetic waves, or man-made chemicals. He argued that none of these reports are supported by robust evidence.

Instead, he believes there is strong evidence suggesting that infection later in childhood, in the absence of earlier priming, can trigger ALL.

Dr Greaves’ studies of identical twins with ALL showed that 2 mutations were required for ALL development. The first arises in one twin in the womb but produces a population of pre-malignant cells that spread to the other twin via their shared blood supply. The second mutation arises after birth and is different in the twins.

Population studies and animal experiments suggest this second genetic hit can be triggered by infection, probably by a range of common viruses and bacteria. In one unique cluster of cases investigated by Dr Greaves and his colleagues, all cases were infected with flu virus.

In other work, researchers engineered mice with an active leukemia-initiating gene. When the team moved the mice from an ultra-clean, germ-free environment to one that had common microbes, the mice developed ALL.

Population studies have indicated that early exposure to infection in infancy, such as via day care attendance and breast feeding, can protect against ALL, probably by priming the immune system. This suggests childhood ALL may be preventable.

Dr Greaves is now investigating whether earlier exposure to harmless microbes could prevent leukemia in mice.

“I have spent more than 40 years researching childhood leukemia, and, over that time, there has been huge progress in our understanding of its biology and its treatment . . . ,” Dr Greaves said. “But it has always struck me that something big was missing, a gap in our knowledge [that failed to explain] why or how otherwise healthy children develop leukemia and whether this cancer is preventable.”

“This body of research is a culmination of decades of work and at last provides a credible explanation for how the major type of childhood leukemia develops. The research strongly suggests that ALL has a clear biological cause and is triggered by a variety of infections in predisposed children whose immune systems have not been properly primed. It also busts some persistent myths about the causes of leukemia, such as the damaging but unsubstantiated claims that the disease is commonly caused by exposure to electro-magnetic waves or pollution.”

“I hope this research will have a real impact on the lives of children. The most important implication is that most cases of childhood leukemia are likely to be preventable. It might be done in the same way that is currently under consideration for autoimmune disease or allergies, perhaps with simple and safe interventions to expose infants to a variety of common and harmless ‘bugs.’”

Photo by Petr Kratochvil

Childhood acute lymphoblastic leukemia (ALL) may be preventable, according to a researcher.

Mel Greaves, PhD, of The Institute of Cancer Research in London, UK, reviewed more than 30 years of research and concluded that ALL develops in 2 steps—genetic mutation before birth and further genetic change after birth triggered by infection.

The evidence suggests that infection early in life is beneficial to prime the immune system, but later infection without earlier priming can trigger ALL.

So priming the immune system in the first year of life could potentially prevent childhood ALL, according to Dr Greaves.

He outlined this theory in Nature Reviews Cancer.

Dr Greaves compiled more than 30 years of research into genetics, cell biology, immunology, epidemiology, and animal modelling of ALL.

The evidence led him to conclude that ALL begins with a genetic mutation that occurs before birth and predisposes a child to leukemia.

The disease is triggered later, in childhood, by exposure to one or more common infections. This primarily occurs in children who experienced “clean” childhoods in their first year of life, without much interaction with other infants or older children.

Dr Greaves challenged previous reports of possible environmental causes for ALL, such as ionizing radiation, electromagnetic waves, or man-made chemicals. He argued that none of these reports are supported by robust evidence.

Instead, he believes there is strong evidence suggesting that infection later in childhood, in the absence of earlier priming, can trigger ALL.

Dr Greaves’ studies of identical twins with ALL showed that 2 mutations were required for ALL development. The first arises in one twin in the womb but produces a population of pre-malignant cells that spread to the other twin via their shared blood supply. The second mutation arises after birth and is different in the twins.

Population studies and animal experiments suggest this second genetic hit can be triggered by infection, probably by a range of common viruses and bacteria. In one unique cluster of cases investigated by Dr Greaves and his colleagues, all cases were infected with flu virus.

In other work, researchers engineered mice with an active leukemia-initiating gene. When the team moved the mice from an ultra-clean, germ-free environment to one that had common microbes, the mice developed ALL.

Population studies have indicated that early exposure to infection in infancy, such as via day care attendance and breast feeding, can protect against ALL, probably by priming the immune system. This suggests childhood ALL may be preventable.

Dr Greaves is now investigating whether earlier exposure to harmless microbes could prevent leukemia in mice.

“I have spent more than 40 years researching childhood leukemia, and, over that time, there has been huge progress in our understanding of its biology and its treatment . . . ,” Dr Greaves said. “But it has always struck me that something big was missing, a gap in our knowledge [that failed to explain] why or how otherwise healthy children develop leukemia and whether this cancer is preventable.”

“This body of research is a culmination of decades of work and at last provides a credible explanation for how the major type of childhood leukemia develops. The research strongly suggests that ALL has a clear biological cause and is triggered by a variety of infections in predisposed children whose immune systems have not been properly primed. It also busts some persistent myths about the causes of leukemia, such as the damaging but unsubstantiated claims that the disease is commonly caused by exposure to electro-magnetic waves or pollution.”

“I hope this research will have a real impact on the lives of children. The most important implication is that most cases of childhood leukemia are likely to be preventable. It might be done in the same way that is currently under consideration for autoimmune disease or allergies, perhaps with simple and safe interventions to expose infants to a variety of common and harmless ‘bugs.’”

Photo from Business Wire

GLASGOW—Final results from the HAVEN 3 study suggest emicizumab prophylaxis can reduce bleeding in hemophilia A patients without factor VIII inhibitors.

Compared to patients who did not receive prophylaxis, those who received emicizumab prophylaxis had a 96% to 97% reduction in treated bleeds and a 94% to 95% reduction in all bleeds.

An intra-patient comparison showed a 68% reduction in treated bleeds with once-weekly emicizumab, compared to prior factor VIII prophylaxis.

“[Emicizumab] is the first medicine to show superior efficacy to prior factor VIII prophylaxis, the current standard of care therapy, as demonstrated by a statistically significant reduction in treated bleeds in the HAVEN 3 study intra-patient comparison,” said Johnny Mahlangu, MB BCh, of the University of the Witwatersrand in Johannesburg, South Africa.

Dr Mahlangu presented these results at the World Federation of Hemophilia (WFH) 2018 World Congress during the late-breaking abstract session on Monday. HAVEN 3 was sponsored by Hoffmann-La Roche.

Patients and treatment

In this phase 3 trial, researchers evaluated emicizumab in patients with hemophilia A without factor VIII inhibitors. The study included 152 patients who were 12 years of age or older and were previously treated with factor VIII therapy on-demand or as prophylaxis.

Patients previously treated with on-demand factor VIII were randomized in a 2:2:1 fashion to receive:

• Emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study (arm A, n=36)
• Emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 3 mg/kg/2wks for at least 24 weeks (arm B, n=35)
• No prophylaxis, only episodic/on-demand factor VIII treatment (arm C, n=18).

Patients previously treated with factor VIII prophylaxis received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study (arm D, n=63).

Episodic treatment of breakthrough bleeds with factor VIII therapy was allowed per protocol.

Emicizumab vs no prophylaxis

The model-based (negative binomial regression model) annualized bleeding rate (ABR) for treated bleeds was 1.5 in arm A, 1.3 in arm B, and 38.2 in arm C. The median ABR for treated bleeds was 0 in arms A and B and 40.4 in arm C.

Compared to patients in arm C, those in arm A had a 96% (P<0.0001) reduction in treated bleeds, and those in arm B had a 97% (P<0.0001) reduction in treated bleeds.

None of the patients in arm C had 0 treated bleeds, compared to 55.6% of patients in arm A and 60% of patients in arm B.

The model-based ABR for all bleeds was 2.5 in arm A, 2.6 in arm B, and 47.6 in arm C.

Patients in arm A had a 95% reduction in all bleeds (P<0.0001), and patients in arm B had a 94% reduction in all bleeds (P<0.0001), compared to patients in arm C.

Fifty percent of patients in arm A had 0 total bleeds, as did 40% of patients in arm B and 0% of patients in arm C.

Intra-patient comparison

The researchers compared previous prophylaxis to once-weekly emicizumab prophylaxis in 48 patients from arm D.

The model-based ABR for treated bleeds was 4.8 with prior prophylaxis and 1.5 with emicizumab. The median ABR for treated bleeds was 1.8 and 0.0, respectively.

Patients had a 68% reduction in treated bleeds with emicizumab (P<0.0001).

With prior prophylaxis, 39.6% of patients had 0 treated bleeds. With emicizumab, 54.2% of patients had 0 treated bleeds.

Safety

There were no serious adverse events (AEs) related to emicizumab, no anti-drug antibodies detected, and none of the patients on emicizumab developed de novo factor VIII inhibitors.

Injection-site reactions occurred in 25.3% of all patients (38/150), 25% of patients in arm A (9/36), 20% in arm B (7/35), 12.5% in arm C (2/16), and 31.7% in arm D (20/63).

An additional patient in arm D (who was included in the total) reported an “injection-site erythema,” not an “injection-site reaction.”

Upper respiratory tract infections occurred in 10.7% of all patients (n=16), 11.1% (n=4) of those in arm A, 11.4% (n=4) of those in arm B, 0% of those in arm C, and 12.7% (n=8) of those in arm D.

Other AEs occurring in at least 5% of patients were arthralgia (19%), nasopharyngitis (12%), headache (11%), and influenza (6%).

One patient in arm B discontinued emicizumab due to multiple mild AEs—insomnia, hair loss, nightmare, lethargy, depressed mood, headache, and pruritus.

Two patients were lost to follow-up—1 in arm A and 1 in arm C.

Photo from Business Wire

GLASGOW—Final results from the HAVEN 3 study suggest emicizumab prophylaxis can reduce bleeding in hemophilia A patients without factor VIII inhibitors.

Compared to patients who did not receive prophylaxis, those who received emicizumab prophylaxis had a 96% to 97% reduction in treated bleeds and a 94% to 95% reduction in all bleeds.

An intra-patient comparison showed a 68% reduction in treated bleeds with once-weekly emicizumab, compared to prior factor VIII prophylaxis.

“[Emicizumab] is the first medicine to show superior efficacy to prior factor VIII prophylaxis, the current standard of care therapy, as demonstrated by a statistically significant reduction in treated bleeds in the HAVEN 3 study intra-patient comparison,” said Johnny Mahlangu, MB BCh, of the University of the Witwatersrand in Johannesburg, South Africa.

Dr Mahlangu presented these results at the World Federation of Hemophilia (WFH) 2018 World Congress during the late-breaking abstract session on Monday. HAVEN 3 was sponsored by Hoffmann-La Roche.

Patients and treatment

In this phase 3 trial, researchers evaluated emicizumab in patients with hemophilia A without factor VIII inhibitors. The study included 152 patients who were 12 years of age or older and were previously treated with factor VIII therapy on-demand or as prophylaxis.

Patients previously treated with on-demand factor VIII were randomized in a 2:2:1 fashion to receive:

• Emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study (arm A, n=36)
• Emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 3 mg/kg/2wks for at least 24 weeks (arm B, n=35)
• No prophylaxis, only episodic/on-demand factor VIII treatment (arm C, n=18).

Patients previously treated with factor VIII prophylaxis received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study (arm D, n=63).

Episodic treatment of breakthrough bleeds with factor VIII therapy was allowed per protocol.

Emicizumab vs no prophylaxis

The model-based (negative binomial regression model) annualized bleeding rate (ABR) for treated bleeds was 1.5 in arm A, 1.3 in arm B, and 38.2 in arm C. The median ABR for treated bleeds was 0 in arms A and B and 40.4 in arm C.

Compared to patients in arm C, those in arm A had a 96% (P<0.0001) reduction in treated bleeds, and those in arm B had a 97% (P<0.0001) reduction in treated bleeds.

None of the patients in arm C had 0 treated bleeds, compared to 55.6% of patients in arm A and 60% of patients in arm B.

The model-based ABR for all bleeds was 2.5 in arm A, 2.6 in arm B, and 47.6 in arm C.

Patients in arm A had a 95% reduction in all bleeds (P<0.0001), and patients in arm B had a 94% reduction in all bleeds (P<0.0001), compared to patients in arm C.

Fifty percent of patients in arm A had 0 total bleeds, as did 40% of patients in arm B and 0% of patients in arm C.

Intra-patient comparison

The researchers compared previous prophylaxis to once-weekly emicizumab prophylaxis in 48 patients from arm D.

The model-based ABR for treated bleeds was 4.8 with prior prophylaxis and 1.5 with emicizumab. The median ABR for treated bleeds was 1.8 and 0.0, respectively.

Patients had a 68% reduction in treated bleeds with emicizumab (P<0.0001).

With prior prophylaxis, 39.6% of patients had 0 treated bleeds. With emicizumab, 54.2% of patients had 0 treated bleeds.

Safety

There were no serious adverse events (AEs) related to emicizumab, no anti-drug antibodies detected, and none of the patients on emicizumab developed de novo factor VIII inhibitors.

Injection-site reactions occurred in 25.3% of all patients (38/150), 25% of patients in arm A (9/36), 20% in arm B (7/35), 12.5% in arm C (2/16), and 31.7% in arm D (20/63).

An additional patient in arm D (who was included in the total) reported an “injection-site erythema,” not an “injection-site reaction.”

Upper respiratory tract infections occurred in 10.7% of all patients (n=16), 11.1% (n=4) of those in arm A, 11.4% (n=4) of those in arm B, 0% of those in arm C, and 12.7% (n=8) of those in arm D.

Other AEs occurring in at least 5% of patients were arthralgia (19%), nasopharyngitis (12%), headache (11%), and influenza (6%).

One patient in arm B discontinued emicizumab due to multiple mild AEs—insomnia, hair loss, nightmare, lethargy, depressed mood, headache, and pruritus.

Two patients were lost to follow-up—1 in arm A and 1 in arm C.

Photo from Business Wire

GLASGOW—Final results from the HAVEN 3 study suggest emicizumab prophylaxis can reduce bleeding in hemophilia A patients without factor VIII inhibitors.

Compared to patients who did not receive prophylaxis, those who received emicizumab prophylaxis had a 96% to 97% reduction in treated bleeds and a 94% to 95% reduction in all bleeds.

An intra-patient comparison showed a 68% reduction in treated bleeds with once-weekly emicizumab, compared to prior factor VIII prophylaxis.

“[Emicizumab] is the first medicine to show superior efficacy to prior factor VIII prophylaxis, the current standard of care therapy, as demonstrated by a statistically significant reduction in treated bleeds in the HAVEN 3 study intra-patient comparison,” said Johnny Mahlangu, MB BCh, of the University of the Witwatersrand in Johannesburg, South Africa.

Dr Mahlangu presented these results at the World Federation of Hemophilia (WFH) 2018 World Congress during the late-breaking abstract session on Monday. HAVEN 3 was sponsored by Hoffmann-La Roche.

Patients and treatment

In this phase 3 trial, researchers evaluated emicizumab in patients with hemophilia A without factor VIII inhibitors. The study included 152 patients who were 12 years of age or older and were previously treated with factor VIII therapy on-demand or as prophylaxis.

Patients previously treated with on-demand factor VIII were randomized in a 2:2:1 fashion to receive:

• Emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study (arm A, n=36)
• Emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 3 mg/kg/2wks for at least 24 weeks (arm B, n=35)
• No prophylaxis, only episodic/on-demand factor VIII treatment (arm C, n=18).

Patients previously treated with factor VIII prophylaxis received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study (arm D, n=63).

Episodic treatment of breakthrough bleeds with factor VIII therapy was allowed per protocol.

Emicizumab vs no prophylaxis

The model-based (negative binomial regression model) annualized bleeding rate (ABR) for treated bleeds was 1.5 in arm A, 1.3 in arm B, and 38.2 in arm C. The median ABR for treated bleeds was 0 in arms A and B and 40.4 in arm C.

Compared to patients in arm C, those in arm A had a 96% (P<0.0001) reduction in treated bleeds, and those in arm B had a 97% (P<0.0001) reduction in treated bleeds.

None of the patients in arm C had 0 treated bleeds, compared to 55.6% of patients in arm A and 60% of patients in arm B.

The model-based ABR for all bleeds was 2.5 in arm A, 2.6 in arm B, and 47.6 in arm C.

Patients in arm A had a 95% reduction in all bleeds (P<0.0001), and patients in arm B had a 94% reduction in all bleeds (P<0.0001), compared to patients in arm C.

Fifty percent of patients in arm A had 0 total bleeds, as did 40% of patients in arm B and 0% of patients in arm C.

Intra-patient comparison

The researchers compared previous prophylaxis to once-weekly emicizumab prophylaxis in 48 patients from arm D.

The model-based ABR for treated bleeds was 4.8 with prior prophylaxis and 1.5 with emicizumab. The median ABR for treated bleeds was 1.8 and 0.0, respectively.

Patients had a 68% reduction in treated bleeds with emicizumab (P<0.0001).

With prior prophylaxis, 39.6% of patients had 0 treated bleeds. With emicizumab, 54.2% of patients had 0 treated bleeds.

Safety

There were no serious adverse events (AEs) related to emicizumab, no anti-drug antibodies detected, and none of the patients on emicizumab developed de novo factor VIII inhibitors.

Injection-site reactions occurred in 25.3% of all patients (38/150), 25% of patients in arm A (9/36), 20% in arm B (7/35), 12.5% in arm C (2/16), and 31.7% in arm D (20/63).

An additional patient in arm D (who was included in the total) reported an “injection-site erythema,” not an “injection-site reaction.”

Upper respiratory tract infections occurred in 10.7% of all patients (n=16), 11.1% (n=4) of those in arm A, 11.4% (n=4) of those in arm B, 0% of those in arm C, and 12.7% (n=8) of those in arm D.

Other AEs occurring in at least 5% of patients were arthralgia (19%), nasopharyngitis (12%), headache (11%), and influenza (6%).

One patient in arm B discontinued emicizumab due to multiple mild AEs—insomnia, hair loss, nightmare, lethargy, depressed mood, headache, and pruritus.

Two patients were lost to follow-up—1 in arm A and 1 in arm C.

Image from Erhabor Osaro

The US Food and Drug Administration (FDA) has approved avatrombopag (DOPTELET®), a second-generation thrombopoietin receptor agonist.

Avatrombopag is now approved to treat thrombocytopenia in adults with chronic liver disease (CLD) who are scheduled to undergo a procedure.

Dova Pharmaceuticals, Inc., plans to launch the drug in June.

The FDA approved avatrombopag based on data from 2 randomized, double-blind, placebo-controlled phase 3 trials—ADAPT-1 (n=231) and ADAPT-2 (n=204).

The trials enrolled adults with thrombocytopenia (platelet count less than 50,000/µL) and CLD.

Patients received 40 mg or 60 mg of avatrombopag daily for 5 days based on their baseline platelet counts (40 to <50,000/mL or <40,000/mL, respectively), or they received placebo.

In both trials, avatrombopag reduced the need for platelet transfusions or rescue procedures for bleeding up to 7 days following a scheduled procedure.

In ADAPT-1, platelet transfusions/rescue procedures were not required for:

• 66% of patients in the 60 mg avatrombopag arm and 23% of matching placebo recipients (P<0.0001)
• 88% of the 40 mg avatrombopag arm and 38% of matching placebo recipients (P<0.0001).

In ADAPT-2, platelet transfusions/rescue procedures were not required for:

• 69% of patients in the 60 mg avatrombopag arm and 35% of matching placebo recipients (P=0.0006)
• 88% of the 40 mg avatrombopag arm and 33% of placebo recipients (P<0.0001).

The most common adverse events (AEs) in both trials (in the avatrombopag and placebo groups, respectively) were pyrexia (10% and 9%), abdominal pain (7% and 6%), nausea (7% for both), headache (6% for both), fatigue (4% and 3%), and peripheral edema (3% and 2%).

The incidence of serious AEs was 7% in the 60 mg avatrombopag group and 13% in the matching placebo group. The incidence was 8% in the 40 mg avatrombopag group and 3% in the matching placebo group.

The most common serious AE reported with avatrombopag was hyponatremia, occurring in 2 patients (0.7%).

AEs resulting in discontinuation of avatrombopag were anemia, pyrexia, and myalgia. Each of these events was reported in a single (0.4%) patient in the avatrombopag 60 mg group.

Additional data from ADAPT-1 and ADAPT-2 are available in the prescribing information for avatrombopag, which can be found at www.doptelet.com.

Image from Erhabor Osaro

The US Food and Drug Administration (FDA) has approved avatrombopag (DOPTELET®), a second-generation thrombopoietin receptor agonist.

Avatrombopag is now approved to treat thrombocytopenia in adults with chronic liver disease (CLD) who are scheduled to undergo a procedure.

Dova Pharmaceuticals, Inc., plans to launch the drug in June.

The FDA approved avatrombopag based on data from 2 randomized, double-blind, placebo-controlled phase 3 trials—ADAPT-1 (n=231) and ADAPT-2 (n=204).

The trials enrolled adults with thrombocytopenia (platelet count less than 50,000/µL) and CLD.

Patients received 40 mg or 60 mg of avatrombopag daily for 5 days based on their baseline platelet counts (40 to <50,000/mL or <40,000/mL, respectively), or they received placebo.

In both trials, avatrombopag reduced the need for platelet transfusions or rescue procedures for bleeding up to 7 days following a scheduled procedure.

In ADAPT-1, platelet transfusions/rescue procedures were not required for:

• 66% of patients in the 60 mg avatrombopag arm and 23% of matching placebo recipients (P<0.0001)
• 88% of the 40 mg avatrombopag arm and 38% of matching placebo recipients (P<0.0001).

In ADAPT-2, platelet transfusions/rescue procedures were not required for:

• 69% of patients in the 60 mg avatrombopag arm and 35% of matching placebo recipients (P=0.0006)
• 88% of the 40 mg avatrombopag arm and 33% of placebo recipients (P<0.0001).

The most common adverse events (AEs) in both trials (in the avatrombopag and placebo groups, respectively) were pyrexia (10% and 9%), abdominal pain (7% and 6%), nausea (7% for both), headache (6% for both), fatigue (4% and 3%), and peripheral edema (3% and 2%).

The incidence of serious AEs was 7% in the 60 mg avatrombopag group and 13% in the matching placebo group. The incidence was 8% in the 40 mg avatrombopag group and 3% in the matching placebo group.

The most common serious AE reported with avatrombopag was hyponatremia, occurring in 2 patients (0.7%).

AEs resulting in discontinuation of avatrombopag were anemia, pyrexia, and myalgia. Each of these events was reported in a single (0.4%) patient in the avatrombopag 60 mg group.

Additional data from ADAPT-1 and ADAPT-2 are available in the prescribing information for avatrombopag, which can be found at www.doptelet.com.

Image from Erhabor Osaro

The US Food and Drug Administration (FDA) has approved avatrombopag (DOPTELET®), a second-generation thrombopoietin receptor agonist.

Avatrombopag is now approved to treat thrombocytopenia in adults with chronic liver disease (CLD) who are scheduled to undergo a procedure.

Dova Pharmaceuticals, Inc., plans to launch the drug in June.

The FDA approved avatrombopag based on data from 2 randomized, double-blind, placebo-controlled phase 3 trials—ADAPT-1 (n=231) and ADAPT-2 (n=204).

The trials enrolled adults with thrombocytopenia (platelet count less than 50,000/µL) and CLD.

Patients received 40 mg or 60 mg of avatrombopag daily for 5 days based on their baseline platelet counts (40 to <50,000/mL or <40,000/mL, respectively), or they received placebo.

In both trials, avatrombopag reduced the need for platelet transfusions or rescue procedures for bleeding up to 7 days following a scheduled procedure.

In ADAPT-1, platelet transfusions/rescue procedures were not required for:

• 66% of patients in the 60 mg avatrombopag arm and 23% of matching placebo recipients (P<0.0001)
• 88% of the 40 mg avatrombopag arm and 38% of matching placebo recipients (P<0.0001).

In ADAPT-2, platelet transfusions/rescue procedures were not required for:

• 69% of patients in the 60 mg avatrombopag arm and 35% of matching placebo recipients (P=0.0006)
• 88% of the 40 mg avatrombopag arm and 33% of placebo recipients (P<0.0001).

The most common adverse events (AEs) in both trials (in the avatrombopag and placebo groups, respectively) were pyrexia (10% and 9%), abdominal pain (7% and 6%), nausea (7% for both), headache (6% for both), fatigue (4% and 3%), and peripheral edema (3% and 2%).

The incidence of serious AEs was 7% in the 60 mg avatrombopag group and 13% in the matching placebo group. The incidence was 8% in the 40 mg avatrombopag group and 3% in the matching placebo group.

The most common serious AE reported with avatrombopag was hyponatremia, occurring in 2 patients (0.7%).

AEs resulting in discontinuation of avatrombopag were anemia, pyrexia, and myalgia. Each of these events was reported in a single (0.4%) patient in the avatrombopag 60 mg group.

Additional data from ADAPT-1 and ADAPT-2 are available in the prescribing information for avatrombopag, which can be found at www.doptelet.com.

Boston is my hometown and I can’t wait to show it off at our Vascular Annual Meeting.

Come join me there June 20-23 for the preeminent educational and social networking event of the year in vascular surgery. Scientific sessions will be June 21-23 and the Exhibit Hall will be open June 21-22.

All scientific meetings, educational sessions, and exhibits will be at the Hynes Convention Center. Committee meetings, the SVS Board of Directors meeting, and alumni and committee receptions will be held at the Sheraton Boston Hotel, the VAM headquarters hotel. Other hotel options are available. (See vsweb.org/hotels18.) Special room rates were to end May 22, so it’s possible you may need to make your own housing arrangements.

This year’s VAM is all about the vascular team. In fact, that’s the theme: “Home of the Vascular Team – Partners in Patient Care.” There are sessions for the whole team – surgeons, nurses, nurse practitioners, technologists, and physician assistants. We have special programming for PAs on Thursday afternoon, and the Vascular Quality Initiative and the Society for Vascular Nursing are holding their annual sessions in tandem with VAM.

Creating the program followed extensive surveying after the 2017 meeting. In response to member feedback, this year we are highlighting:

• Topics and practical sessions for community practitioners and young surgeons, including on clinical practice guidelines, practice management, even physician burnout.
• More opportunities to interact with presenters, particularly with the “Tips & Tricks” and “Ask the Experts” daily sessions.
• Ideas and translational research that participants can take home to their practices.
• VAM on Demand, letting you catch up on missed sessions afterwards, plus the VAM Planner and a new mobile app to help everyone design their own meetings and navigate VAM easily.

The familiar favorites will be there: workshops, concurrent and scientific sessions, postgraduate courses – free to SVS members, a $300 value – events for international members, collaborative sessions with other societies, plenty of opportunities to network and connect with friends and colleagues, and educational credits, not to mention the chance to explore the fascinating city I’ve always loved.

We have a great mix of old activities and some new initiatives. And we’re excited for you to experience it all at VAM 2018. See you in Beantown. 

Boston is my hometown and I can’t wait to show it off at our Vascular Annual Meeting.

Come join me there June 20-23 for the preeminent educational and social networking event of the year in vascular surgery. Scientific sessions will be June 21-23 and the Exhibit Hall will be open June 21-22.

All scientific meetings, educational sessions, and exhibits will be at the Hynes Convention Center. Committee meetings, the SVS Board of Directors meeting, and alumni and committee receptions will be held at the Sheraton Boston Hotel, the VAM headquarters hotel. Other hotel options are available. (See vsweb.org/hotels18.) Special room rates were to end May 22, so it’s possible you may need to make your own housing arrangements.

This year’s VAM is all about the vascular team. In fact, that’s the theme: “Home of the Vascular Team – Partners in Patient Care.” There are sessions for the whole team – surgeons, nurses, nurse practitioners, technologists, and physician assistants. We have special programming for PAs on Thursday afternoon, and the Vascular Quality Initiative and the Society for Vascular Nursing are holding their annual sessions in tandem with VAM.

Creating the program followed extensive surveying after the 2017 meeting. In response to member feedback, this year we are highlighting:

• Topics and practical sessions for community practitioners and young surgeons, including on clinical practice guidelines, practice management, even physician burnout.
• More opportunities to interact with presenters, particularly with the “Tips & Tricks” and “Ask the Experts” daily sessions.
• Ideas and translational research that participants can take home to their practices.
• VAM on Demand, letting you catch up on missed sessions afterwards, plus the VAM Planner and a new mobile app to help everyone design their own meetings and navigate VAM easily.

The familiar favorites will be there: workshops, concurrent and scientific sessions, postgraduate courses – free to SVS members, a $300 value – events for international members, collaborative sessions with other societies, plenty of opportunities to network and connect with friends and colleagues, and educational credits, not to mention the chance to explore the fascinating city I’ve always loved.

We have a great mix of old activities and some new initiatives. And we’re excited for you to experience it all at VAM 2018. See you in Beantown. 

Boston is my hometown and I can’t wait to show it off at our Vascular Annual Meeting.

Come join me there June 20-23 for the preeminent educational and social networking event of the year in vascular surgery. Scientific sessions will be June 21-23 and the Exhibit Hall will be open June 21-22.

All scientific meetings, educational sessions, and exhibits will be at the Hynes Convention Center. Committee meetings, the SVS Board of Directors meeting, and alumni and committee receptions will be held at the Sheraton Boston Hotel, the VAM headquarters hotel. Other hotel options are available. (See vsweb.org/hotels18.) Special room rates were to end May 22, so it’s possible you may need to make your own housing arrangements.

This year’s VAM is all about the vascular team. In fact, that’s the theme: “Home of the Vascular Team – Partners in Patient Care.” There are sessions for the whole team – surgeons, nurses, nurse practitioners, technologists, and physician assistants. We have special programming for PAs on Thursday afternoon, and the Vascular Quality Initiative and the Society for Vascular Nursing are holding their annual sessions in tandem with VAM.

Creating the program followed extensive surveying after the 2017 meeting. In response to member feedback, this year we are highlighting:

• Topics and practical sessions for community practitioners and young surgeons, including on clinical practice guidelines, practice management, even physician burnout.
• More opportunities to interact with presenters, particularly with the “Tips & Tricks” and “Ask the Experts” daily sessions.
• Ideas and translational research that participants can take home to their practices.
• VAM on Demand, letting you catch up on missed sessions afterwards, plus the VAM Planner and a new mobile app to help everyone design their own meetings and navigate VAM easily.

The familiar favorites will be there: workshops, concurrent and scientific sessions, postgraduate courses – free to SVS members, a $300 value – events for international members, collaborative sessions with other societies, plenty of opportunities to network and connect with friends and colleagues, and educational credits, not to mention the chance to explore the fascinating city I’ve always loved.

We have a great mix of old activities and some new initiatives. And we’re excited for you to experience it all at VAM 2018. See you in Beantown. 

Association between hospitalist years of experience with mortality in hospitalized patients

Cohort study showed that Medicare patients cared for by hospitalists in their first year of practice experienced higher in-hospital and 30-day mortality, compared with patients cared for by hospitalists in their second year of practice. New hospitalists may need additional monitoring and support to ensure optimal patient outcomes.

Standardized handoff improves preparedness in the ICU

Cluster randomized stepped-wedge trial in eight ICUs in an academic center showed that a standardized handoff intervention was associated with a statistically significant reduction in the odds of clinician self-reported unpreparedness from a poor-quality handoff (odds ratio, 0.19; 95% confidence interval, 0.03-0.74; P = .03).

Citation: Parent B et al. Effect of standardized handoff curriculum on improved clinician preparedness in the intensive care: A stepped-wedge cluster randomized clinical trial. JAMA Surg. 2018 Jan 3. doi: 10.1001/jamasurg.2017.5440.

Association between hospitalist years of experience with mortality in hospitalized patients

Cohort study showed that Medicare patients cared for by hospitalists in their first year of practice experienced higher in-hospital and 30-day mortality, compared with patients cared for by hospitalists in their second year of practice. New hospitalists may need additional monitoring and support to ensure optimal patient outcomes.

Standardized handoff improves preparedness in the ICU

Cluster randomized stepped-wedge trial in eight ICUs in an academic center showed that a standardized handoff intervention was associated with a statistically significant reduction in the odds of clinician self-reported unpreparedness from a poor-quality handoff (odds ratio, 0.19; 95% confidence interval, 0.03-0.74; P = .03).

Citation: Parent B et al. Effect of standardized handoff curriculum on improved clinician preparedness in the intensive care: A stepped-wedge cluster randomized clinical trial. JAMA Surg. 2018 Jan 3. doi: 10.1001/jamasurg.2017.5440.

Association between hospitalist years of experience with mortality in hospitalized patients

Cohort study showed that Medicare patients cared for by hospitalists in their first year of practice experienced higher in-hospital and 30-day mortality, compared with patients cared for by hospitalists in their second year of practice. New hospitalists may need additional monitoring and support to ensure optimal patient outcomes.

Standardized handoff improves preparedness in the ICU

Cluster randomized stepped-wedge trial in eight ICUs in an academic center showed that a standardized handoff intervention was associated with a statistically significant reduction in the odds of clinician self-reported unpreparedness from a poor-quality handoff (odds ratio, 0.19; 95% confidence interval, 0.03-0.74; P = .03).

Citation: Parent B et al. Effect of standardized handoff curriculum on improved clinician preparedness in the intensive care: A stepped-wedge cluster randomized clinical trial. JAMA Surg. 2018 Jan 3. doi: 10.1001/jamasurg.2017.5440.

BOSTON – Positive results from a confirmatory trial appear to put the Optimizer by Impulse Dynamics, a cardiac contractility modulation (CCM) device for patients with function-limiting heart failure, on track for imminent U.S. marketing approval by the Food and Drug Administration. If that happens, several hundreds of thousands of U.S. heart failure patients would immediately become candidates for this treatment based on the enrolled study populations, the benefits shown, and current treatment options for advanced heart failure, experts predicted.

Mitchel L. Zoler/MDedge News

Mitchel L. Zoler/MDedge News

Mitchel L. Zoler/MDedge News

Mitchel L. Zoler/MDedge News

[email protected]

SOURCE: Abraham W et al. Heart Rhythm 2018, Abstract B-LBCT01-02.

BOSTON – Positive results from a confirmatory trial appear to put the Optimizer by Impulse Dynamics, a cardiac contractility modulation (CCM) device for patients with function-limiting heart failure, on track for imminent U.S. marketing approval by the Food and Drug Administration. If that happens, several hundreds of thousands of U.S. heart failure patients would immediately become candidates for this treatment based on the enrolled study populations, the benefits shown, and current treatment options for advanced heart failure, experts predicted.

Mitchel L. Zoler/MDedge News

Mitchel L. Zoler/MDedge News

Mitchel L. Zoler/MDedge News

Mitchel L. Zoler/MDedge News

[email protected]

SOURCE: Abraham W et al. Heart Rhythm 2018, Abstract B-LBCT01-02.

BOSTON – Positive results from a confirmatory trial appear to put the Optimizer by Impulse Dynamics, a cardiac contractility modulation (CCM) device for patients with function-limiting heart failure, on track for imminent U.S. marketing approval by the Food and Drug Administration. If that happens, several hundreds of thousands of U.S. heart failure patients would immediately become candidates for this treatment based on the enrolled study populations, the benefits shown, and current treatment options for advanced heart failure, experts predicted.

Mitchel L. Zoler/MDedge News

Mitchel L. Zoler/MDedge News

Mitchel L. Zoler/MDedge News

Mitchel L. Zoler/MDedge News

[email protected]

SOURCE: Abraham W et al. Heart Rhythm 2018, Abstract B-LBCT01-02.

LIVERPOOL, ENGLAND – Osteoarthritis is associated with a “considerably higher disease burden” than rheumatoid arthritis 6 months after initial presentation, according to one expert’s analysis at the World Congress on Osteoarthritis.

This may partly be because of the improved treatments now available for rheumatoid arthritis, whereas there remain few treatments, and no disease-modifying therapy as yet, for osteoarthritis, Theodore Pincus, MD, suggested at the congress sponsored by the Osteoarthritis Research Society International.

The MDHAQ/RAPID3 is a simple assessment tool that consists of two pages and asks patients to rate items such as their physical function in activities of daily living and levels of pain in the past week. It also asks about levels of anxiety, depression, and quality of sleep, and it includes a self-reported joint count and a patient global assessment. Scores on RAPID3 range from 0 to 30, and comprise three 0-10 scores for physical function, pain, and patient global assessment subscales in which higher scores indicate greater disease burden.

“Using this tool, we’ve been able to obtain data on patients with OA and RA for at least 30 years,” Dr. Pincus said.

One of the issues with comparing the burden of the two diseases, he noted, is that there are few places that have used the same assessment tool.

Dr. Pincus and his associates at Rush University have also shown that the disease burden in OA remains high 6 months after first visit, while greater improvement is seen in RA over this period (Osteoarthritis Cartilage. 2018;26[1]:S260. Abstract 491).

In a study of 151 patients with OA and 202 with RA, they found the composite RAPID3 scores were equally high in patients with OA and RA at their first visit (16.0 vs. 15.5, respectively) but higher in OA patients at the 6-month reassessment (14.3 vs. 11.9; P less than .004).

“We can now say that at presentation, OA and RA are similar in MDHAQ/RAPID3 scores, which were adjusted for age and BMI,” Dr. Pincus said. “Both the OA and RA patients improved, but considerably greater improvement in RA versus OA resulted in significantly poorer status for OA versus RA at 6 months.”

However, that’s not to say that OA is a worse disease than RA in every patient, Dr. Pincus was keen to point out. “Some patients with each disease have mild, moderate, or severe disease,” he stated. RA is used as benchmark for a severe disease, so these data highlight that “OA is a severe disease as well.”

This sentiment was the focus of a 2016 white paper produced by OARSI and submitted to the Food and Drug Administration, which states the case for the need to take OA more seriously and for regulatory restrictions to be removed to enable new treatments to be developed.

The prevalence of OA is at least 10-20 times higher than RA, and it’s likely that a large percentage of OA patients never get to see a rheumatologist, Dr. Pincus said. Yet the resources that go into managing RA are far greater if one excludes joint replacement.

Dr. Pincus noted that RA was not always regarded as a severe disease: 30 years ago the textbooks were stating that it had a good prognosis in the majority of cases and that patients could, by and large, use conservative regimens to manage their disease. However, real-world evidence showed that RA was associated with severe declines in function, high levels of work disability, and increased mortality, Dr. Pincus observed.

“Is osteoarthritis in 2018 where rheumatoid arthritis was in 1988, 30 years ago?” he asked rhetorically.

“The risk of long-term mortality in RA, OA, and most rheumatic disease is similar to, or greater than, hypertension, diabetes, as well as many cardiovascular and neoplastic diseases,” Dr. Pincus continued. Whereas mechanisms exist to try to log all cancer cases and compile data on the number of deaths, a rheumatic disease often is not listed anywhere on the death certificate, even as contributing to mortality, as rheumatic diseases generally are not the acute cause of death.

Functional disability and socioeconomic status are more important predictors of work disability and mortality than “any biomarker or imaging data, except x-ray.” Perhaps, Dr. Pincus said, these could also be important indicators of poor prognosis in OA and all chronic diseases?

“Physical function is a big deal,” he said. Data from a study looking at adults over the age of 50 years in the general Finnish population showed 5-year survival was significantly reduced by poorer functional capacity and less frequent physical exercise, at levels higher than smoking. Perhaps, the musculoskeletal system is more important than the other organs of the body for maintaining health, Dr. Pincus suggested.

Assessing functional status with tools such as the MDHAQ/RAPID3 is “really useful” in daily practice, Dr. Pincus said. He concluded with the words of Rudolph Virchow, who observed more than 100 years ago, that “the improvement of medicine would eventually prolong human life, but improvement of social conditions could achieve this result now and more rapidly and successfully.”

Dr. Pincus is the president of Medical History Services, which receives royalties and license fees from copyright and trademark of MDHAQ, RAPID3, or both, all of which are used to support further development of quantitative clinical measurement by both patients and physicians. He holds stock in the company and has received research funding from the company. Dr. Pincus also disclosed having a consulting agreement with Lilly.

SOURCE: Pincus T et al. Osteoarthritis Cartilage. 2018:26(1):S4. Abstract I-11.

*This story was updated 5/24/2018.

LIVERPOOL, ENGLAND – Osteoarthritis is associated with a “considerably higher disease burden” than rheumatoid arthritis 6 months after initial presentation, according to one expert’s analysis at the World Congress on Osteoarthritis.

This may partly be because of the improved treatments now available for rheumatoid arthritis, whereas there remain few treatments, and no disease-modifying therapy as yet, for osteoarthritis, Theodore Pincus, MD, suggested at the congress sponsored by the Osteoarthritis Research Society International.

The MDHAQ/RAPID3 is a simple assessment tool that consists of two pages and asks patients to rate items such as their physical function in activities of daily living and levels of pain in the past week. It also asks about levels of anxiety, depression, and quality of sleep, and it includes a self-reported joint count and a patient global assessment. Scores on RAPID3 range from 0 to 30, and comprise three 0-10 scores for physical function, pain, and patient global assessment subscales in which higher scores indicate greater disease burden.

“Using this tool, we’ve been able to obtain data on patients with OA and RA for at least 30 years,” Dr. Pincus said.

One of the issues with comparing the burden of the two diseases, he noted, is that there are few places that have used the same assessment tool.

Dr. Pincus and his associates at Rush University have also shown that the disease burden in OA remains high 6 months after first visit, while greater improvement is seen in RA over this period (Osteoarthritis Cartilage. 2018;26[1]:S260. Abstract 491).

In a study of 151 patients with OA and 202 with RA, they found the composite RAPID3 scores were equally high in patients with OA and RA at their first visit (16.0 vs. 15.5, respectively) but higher in OA patients at the 6-month reassessment (14.3 vs. 11.9; P less than .004).

“We can now say that at presentation, OA and RA are similar in MDHAQ/RAPID3 scores, which were adjusted for age and BMI,” Dr. Pincus said. “Both the OA and RA patients improved, but considerably greater improvement in RA versus OA resulted in significantly poorer status for OA versus RA at 6 months.”

However, that’s not to say that OA is a worse disease than RA in every patient, Dr. Pincus was keen to point out. “Some patients with each disease have mild, moderate, or severe disease,” he stated. RA is used as benchmark for a severe disease, so these data highlight that “OA is a severe disease as well.”

This sentiment was the focus of a 2016 white paper produced by OARSI and submitted to the Food and Drug Administration, which states the case for the need to take OA more seriously and for regulatory restrictions to be removed to enable new treatments to be developed.

The prevalence of OA is at least 10-20 times higher than RA, and it’s likely that a large percentage of OA patients never get to see a rheumatologist, Dr. Pincus said. Yet the resources that go into managing RA are far greater if one excludes joint replacement.

Dr. Pincus noted that RA was not always regarded as a severe disease: 30 years ago the textbooks were stating that it had a good prognosis in the majority of cases and that patients could, by and large, use conservative regimens to manage their disease. However, real-world evidence showed that RA was associated with severe declines in function, high levels of work disability, and increased mortality, Dr. Pincus observed.

“Is osteoarthritis in 2018 where rheumatoid arthritis was in 1988, 30 years ago?” he asked rhetorically.

“The risk of long-term mortality in RA, OA, and most rheumatic disease is similar to, or greater than, hypertension, diabetes, as well as many cardiovascular and neoplastic diseases,” Dr. Pincus continued. Whereas mechanisms exist to try to log all cancer cases and compile data on the number of deaths, a rheumatic disease often is not listed anywhere on the death certificate, even as contributing to mortality, as rheumatic diseases generally are not the acute cause of death.

Functional disability and socioeconomic status are more important predictors of work disability and mortality than “any biomarker or imaging data, except x-ray.” Perhaps, Dr. Pincus said, these could also be important indicators of poor prognosis in OA and all chronic diseases?

“Physical function is a big deal,” he said. Data from a study looking at adults over the age of 50 years in the general Finnish population showed 5-year survival was significantly reduced by poorer functional capacity and less frequent physical exercise, at levels higher than smoking. Perhaps, the musculoskeletal system is more important than the other organs of the body for maintaining health, Dr. Pincus suggested.

Assessing functional status with tools such as the MDHAQ/RAPID3 is “really useful” in daily practice, Dr. Pincus said. He concluded with the words of Rudolph Virchow, who observed more than 100 years ago, that “the improvement of medicine would eventually prolong human life, but improvement of social conditions could achieve this result now and more rapidly and successfully.”

Dr. Pincus is the president of Medical History Services, which receives royalties and license fees from copyright and trademark of MDHAQ, RAPID3, or both, all of which are used to support further development of quantitative clinical measurement by both patients and physicians. He holds stock in the company and has received research funding from the company. Dr. Pincus also disclosed having a consulting agreement with Lilly.

SOURCE: Pincus T et al. Osteoarthritis Cartilage. 2018:26(1):S4. Abstract I-11.

*This story was updated 5/24/2018.

LIVERPOOL, ENGLAND – Osteoarthritis is associated with a “considerably higher disease burden” than rheumatoid arthritis 6 months after initial presentation, according to one expert’s analysis at the World Congress on Osteoarthritis.

This may partly be because of the improved treatments now available for rheumatoid arthritis, whereas there remain few treatments, and no disease-modifying therapy as yet, for osteoarthritis, Theodore Pincus, MD, suggested at the congress sponsored by the Osteoarthritis Research Society International.

The MDHAQ/RAPID3 is a simple assessment tool that consists of two pages and asks patients to rate items such as their physical function in activities of daily living and levels of pain in the past week. It also asks about levels of anxiety, depression, and quality of sleep, and it includes a self-reported joint count and a patient global assessment. Scores on RAPID3 range from 0 to 30, and comprise three 0-10 scores for physical function, pain, and patient global assessment subscales in which higher scores indicate greater disease burden.

“Using this tool, we’ve been able to obtain data on patients with OA and RA for at least 30 years,” Dr. Pincus said.

One of the issues with comparing the burden of the two diseases, he noted, is that there are few places that have used the same assessment tool.

Dr. Pincus and his associates at Rush University have also shown that the disease burden in OA remains high 6 months after first visit, while greater improvement is seen in RA over this period (Osteoarthritis Cartilage. 2018;26[1]:S260. Abstract 491).

In a study of 151 patients with OA and 202 with RA, they found the composite RAPID3 scores were equally high in patients with OA and RA at their first visit (16.0 vs. 15.5, respectively) but higher in OA patients at the 6-month reassessment (14.3 vs. 11.9; P less than .004).

“We can now say that at presentation, OA and RA are similar in MDHAQ/RAPID3 scores, which were adjusted for age and BMI,” Dr. Pincus said. “Both the OA and RA patients improved, but considerably greater improvement in RA versus OA resulted in significantly poorer status for OA versus RA at 6 months.”

However, that’s not to say that OA is a worse disease than RA in every patient, Dr. Pincus was keen to point out. “Some patients with each disease have mild, moderate, or severe disease,” he stated. RA is used as benchmark for a severe disease, so these data highlight that “OA is a severe disease as well.”

This sentiment was the focus of a 2016 white paper produced by OARSI and submitted to the Food and Drug Administration, which states the case for the need to take OA more seriously and for regulatory restrictions to be removed to enable new treatments to be developed.

The prevalence of OA is at least 10-20 times higher than RA, and it’s likely that a large percentage of OA patients never get to see a rheumatologist, Dr. Pincus said. Yet the resources that go into managing RA are far greater if one excludes joint replacement.

Dr. Pincus noted that RA was not always regarded as a severe disease: 30 years ago the textbooks were stating that it had a good prognosis in the majority of cases and that patients could, by and large, use conservative regimens to manage their disease. However, real-world evidence showed that RA was associated with severe declines in function, high levels of work disability, and increased mortality, Dr. Pincus observed.

“Is osteoarthritis in 2018 where rheumatoid arthritis was in 1988, 30 years ago?” he asked rhetorically.

“The risk of long-term mortality in RA, OA, and most rheumatic disease is similar to, or greater than, hypertension, diabetes, as well as many cardiovascular and neoplastic diseases,” Dr. Pincus continued. Whereas mechanisms exist to try to log all cancer cases and compile data on the number of deaths, a rheumatic disease often is not listed anywhere on the death certificate, even as contributing to mortality, as rheumatic diseases generally are not the acute cause of death.

Functional disability and socioeconomic status are more important predictors of work disability and mortality than “any biomarker or imaging data, except x-ray.” Perhaps, Dr. Pincus said, these could also be important indicators of poor prognosis in OA and all chronic diseases?

“Physical function is a big deal,” he said. Data from a study looking at adults over the age of 50 years in the general Finnish population showed 5-year survival was significantly reduced by poorer functional capacity and less frequent physical exercise, at levels higher than smoking. Perhaps, the musculoskeletal system is more important than the other organs of the body for maintaining health, Dr. Pincus suggested.

Assessing functional status with tools such as the MDHAQ/RAPID3 is “really useful” in daily practice, Dr. Pincus said. He concluded with the words of Rudolph Virchow, who observed more than 100 years ago, that “the improvement of medicine would eventually prolong human life, but improvement of social conditions could achieve this result now and more rapidly and successfully.”

Dr. Pincus is the president of Medical History Services, which receives royalties and license fees from copyright and trademark of MDHAQ, RAPID3, or both, all of which are used to support further development of quantitative clinical measurement by both patients and physicians. He holds stock in the company and has received research funding from the company. Dr. Pincus also disclosed having a consulting agreement with Lilly.

SOURCE: Pincus T et al. Osteoarthritis Cartilage. 2018:26(1):S4. Abstract I-11.

*This story was updated 5/24/2018.

Roseomonas mucosa bacteria obtained from healthy volunteers without atopic dermatitis reduced the severity of the disorder in a small, early-phase study of 10 adults and 5 children with atopic dermatitis.

The Beginning Assessment of Cutaneous Treatment Efficacy of Roseomonas in Atopic Dermatitis trial; BACTERiAD I/II study, an open-label phase I/II trial, first looked at the therapeutic use of R. mucosa in 10 adults aged 18 years or older. Three sucrose mixtures with increasing doses of live R. mucosa bacteria were topically applied to two body areas – the antecubital fossae and a body surface of their choice – twice per week for 2 weeks per dose. At 6 weeks, the patients stopped using the mixtures and followed a 4-week washout phase.

Treatment was found to reduce mean antecubital SCORAD (SCORing Atopic Dermatitis) scores by 59.8%. Reduction in pruritus was even more pronounced, with a mean decrease of 78.5%. Treating the hands did not improve disease severity, even in patients whose symptoms improved in other body areas. One explanation may be the increased exposure of the hands to topical antimicrobials and environmental exposures, the researchers noted.

With the success in the adult cohort, the researchers enrolled five children aged 7-17 years in the study. These patients were treated twice weekly for 16 weeks. The pediatric patients experienced a mean decrease of 70.3% in their SCORAD scores. The mean decrease in pruritis was 78.8%.

All adults who responded continued to report improved symptoms after the washout period. The pediatric patients are now being evaluated in a washout period.

Four patients did not respond; three of them had a family history of AD persisting into adulthood. “The association between these complex medical histories and the lack of clinical response suggests that differences in heritable host and/or microbial factors may impact treatment responses,” wrote Ian A. Myles, MD, and his colleagues.

“Overall, our findings suggest the safety of topical R. mucosa therapy and justify continuation of our ongoing trial to assess safety and activity in a pediatric cohort of patients with AD. These studies will additionally assess changes in host serum markers, skin metabolomics, and the skin microbiota by culture and genomic methods.”

The researchers noted that expanding to the pediatric population will deepen understanding of topical microbiome transplantation and lay the foundation for placebo-controlled trials to assess efficacy.

This work was supported by the Intramural Research Program of the National Institutes of Allergy and Infectious Diseases and the National Institutes of Health. The researchers had no disclosures.

[email protected]

SOURCE: Myles IA et al. JCI Insight. 2018 May 3. doi: 10.1172/jci.insight.120608.

Roseomonas mucosa bacteria obtained from healthy volunteers without atopic dermatitis reduced the severity of the disorder in a small, early-phase study of 10 adults and 5 children with atopic dermatitis.

The Beginning Assessment of Cutaneous Treatment Efficacy of Roseomonas in Atopic Dermatitis trial; BACTERiAD I/II study, an open-label phase I/II trial, first looked at the therapeutic use of R. mucosa in 10 adults aged 18 years or older. Three sucrose mixtures with increasing doses of live R. mucosa bacteria were topically applied to two body areas – the antecubital fossae and a body surface of their choice – twice per week for 2 weeks per dose. At 6 weeks, the patients stopped using the mixtures and followed a 4-week washout phase.

Treatment was found to reduce mean antecubital SCORAD (SCORing Atopic Dermatitis) scores by 59.8%. Reduction in pruritus was even more pronounced, with a mean decrease of 78.5%. Treating the hands did not improve disease severity, even in patients whose symptoms improved in other body areas. One explanation may be the increased exposure of the hands to topical antimicrobials and environmental exposures, the researchers noted.

With the success in the adult cohort, the researchers enrolled five children aged 7-17 years in the study. These patients were treated twice weekly for 16 weeks. The pediatric patients experienced a mean decrease of 70.3% in their SCORAD scores. The mean decrease in pruritis was 78.8%.

All adults who responded continued to report improved symptoms after the washout period. The pediatric patients are now being evaluated in a washout period.

Four patients did not respond; three of them had a family history of AD persisting into adulthood. “The association between these complex medical histories and the lack of clinical response suggests that differences in heritable host and/or microbial factors may impact treatment responses,” wrote Ian A. Myles, MD, and his colleagues.

“Overall, our findings suggest the safety of topical R. mucosa therapy and justify continuation of our ongoing trial to assess safety and activity in a pediatric cohort of patients with AD. These studies will additionally assess changes in host serum markers, skin metabolomics, and the skin microbiota by culture and genomic methods.”

The researchers noted that expanding to the pediatric population will deepen understanding of topical microbiome transplantation and lay the foundation for placebo-controlled trials to assess efficacy.

This work was supported by the Intramural Research Program of the National Institutes of Allergy and Infectious Diseases and the National Institutes of Health. The researchers had no disclosures.

[email protected]

SOURCE: Myles IA et al. JCI Insight. 2018 May 3. doi: 10.1172/jci.insight.120608.

Roseomonas mucosa bacteria obtained from healthy volunteers without atopic dermatitis reduced the severity of the disorder in a small, early-phase study of 10 adults and 5 children with atopic dermatitis.

The Beginning Assessment of Cutaneous Treatment Efficacy of Roseomonas in Atopic Dermatitis trial; BACTERiAD I/II study, an open-label phase I/II trial, first looked at the therapeutic use of R. mucosa in 10 adults aged 18 years or older. Three sucrose mixtures with increasing doses of live R. mucosa bacteria were topically applied to two body areas – the antecubital fossae and a body surface of their choice – twice per week for 2 weeks per dose. At 6 weeks, the patients stopped using the mixtures and followed a 4-week washout phase.

Treatment was found to reduce mean antecubital SCORAD (SCORing Atopic Dermatitis) scores by 59.8%. Reduction in pruritus was even more pronounced, with a mean decrease of 78.5%. Treating the hands did not improve disease severity, even in patients whose symptoms improved in other body areas. One explanation may be the increased exposure of the hands to topical antimicrobials and environmental exposures, the researchers noted.

With the success in the adult cohort, the researchers enrolled five children aged 7-17 years in the study. These patients were treated twice weekly for 16 weeks. The pediatric patients experienced a mean decrease of 70.3% in their SCORAD scores. The mean decrease in pruritis was 78.8%.

All adults who responded continued to report improved symptoms after the washout period. The pediatric patients are now being evaluated in a washout period.

Four patients did not respond; three of them had a family history of AD persisting into adulthood. “The association between these complex medical histories and the lack of clinical response suggests that differences in heritable host and/or microbial factors may impact treatment responses,” wrote Ian A. Myles, MD, and his colleagues.

“Overall, our findings suggest the safety of topical R. mucosa therapy and justify continuation of our ongoing trial to assess safety and activity in a pediatric cohort of patients with AD. These studies will additionally assess changes in host serum markers, skin metabolomics, and the skin microbiota by culture and genomic methods.”

The researchers noted that expanding to the pediatric population will deepen understanding of topical microbiome transplantation and lay the foundation for placebo-controlled trials to assess efficacy.

This work was supported by the Intramural Research Program of the National Institutes of Allergy and Infectious Diseases and the National Institutes of Health. The researchers had no disclosures.

[email protected]

SOURCE: Myles IA et al. JCI Insight. 2018 May 3. doi: 10.1172/jci.insight.120608.

WASHINGTON – A novel transcatheter mitral valve replacement with a transseptally introduced docking mechanism that secures the valve with native mitral valve leaflets was found feasible and effective in an initial series of 10 patients, according to a first-in-man report at CRT 2018 sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

“All patients remained hemodynamically stable throughout the procedure, and the valve was successfully implanted in all patients,” reported John G. Webb, MD, McLeod Professor of Heart Valve Intervention at the University of British Columbia, Vancouver.

Ted Bosworth/MDedge News

WASHINGTON – A novel transcatheter mitral valve replacement with a transseptally introduced docking mechanism that secures the valve with native mitral valve leaflets was found feasible and effective in an initial series of 10 patients, according to a first-in-man report at CRT 2018 sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

“All patients remained hemodynamically stable throughout the procedure, and the valve was successfully implanted in all patients,” reported John G. Webb, MD, McLeod Professor of Heart Valve Intervention at the University of British Columbia, Vancouver.

Ted Bosworth/MDedge News

WASHINGTON – A novel transcatheter mitral valve replacement with a transseptally introduced docking mechanism that secures the valve with native mitral valve leaflets was found feasible and effective in an initial series of 10 patients, according to a first-in-man report at CRT 2018 sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

“All patients remained hemodynamically stable throughout the procedure, and the valve was successfully implanted in all patients,” reported John G. Webb, MD, McLeod Professor of Heart Valve Intervention at the University of British Columbia, Vancouver.

Ted Bosworth/MDedge News

For patients with non–small-cell lung cancer (NSCLC), preexisting autoimmune disease (AID) does not increase the risk of immune-related adverse events (irAEs) with checkpoint inhibitor therapy, according to investigators.

Flares of AID during therapy were generally mild, and toxicity rates were only slightly increased in patients with AID, they wrote in Journal of Clinical Oncology.

Approximately 14%-25% of patients with lung cancer also have AID, but patients with AID are typically excluded from clinical trials. “This presents a tremendous knowledge gap,” wrote lead author Giulia C. Leonardi, MD, of the Dana-Farber Cancer Institute in Boston, and coauthors.

The retrospective study comprised 56 patients with NSCLC and preexisting autoimmune disease from five academic cancer centers. Almost half of the patients had a rheumatologic disorder, 29% had a dermatologic disorder, 16% had an endocrine disorder, 11% had inflammatory bowel disease, 5% had a neurologic condition, 3% had rheumatic fever, and one patient (2%) had autoimmune hemolytic anemia.

Patients received either a programmed death-1 or programmed death-ligand 1 inhibitor as monotherapy. Median treatment time was 3.1 months, and median follow-up time after starting therapy was 17.5 months.

Eleven percent of patients with preexisting AID developed grade 3 or 4 irAEs, which is similar to 7%-15% of patients in clinical trials. Although 23% of patients experienced a flare of their preexisting AID, these flares were generally mild – no patients discontinued immunotherapy because of a flare. In contrast, 14% of patients halted therapy because of toxicity, a marginally higher number than 3%-8% of patients in trials.

Checkpoint inhibitors are now a mainstay treatment for a lung cancer, including three approved drugs: nivolumab, pembrolizumab, and atezolizumab. “Almost every patient with advanced NSCLC will likely receive a [checkpoint] inhibitor at some point over the course of their disease,” the authors noted. As checkpoint inhibitors may lead to fatal irAEs, the possible interplay between these immunotherapies and AID requires investigation.

“Our study adds to the growing body of evidence supporting the use of immunotherapy in patients with cancer with preexisting AID, albeit with close monitoring for adverse events,” the researchers concluded.

SOURCE: Leonardi GC et al. J Clin Oncol. 2018* May 20. doi: 10.1200/JCO.2017.77.0305.

*Correction, 5/22/18: An earlier version of this article misstated the year in this citation.

For patients with non–small-cell lung cancer (NSCLC), preexisting autoimmune disease (AID) does not increase the risk of immune-related adverse events (irAEs) with checkpoint inhibitor therapy, according to investigators.

Flares of AID during therapy were generally mild, and toxicity rates were only slightly increased in patients with AID, they wrote in Journal of Clinical Oncology.

Approximately 14%-25% of patients with lung cancer also have AID, but patients with AID are typically excluded from clinical trials. “This presents a tremendous knowledge gap,” wrote lead author Giulia C. Leonardi, MD, of the Dana-Farber Cancer Institute in Boston, and coauthors.

The retrospective study comprised 56 patients with NSCLC and preexisting autoimmune disease from five academic cancer centers. Almost half of the patients had a rheumatologic disorder, 29% had a dermatologic disorder, 16% had an endocrine disorder, 11% had inflammatory bowel disease, 5% had a neurologic condition, 3% had rheumatic fever, and one patient (2%) had autoimmune hemolytic anemia.

Patients received either a programmed death-1 or programmed death-ligand 1 inhibitor as monotherapy. Median treatment time was 3.1 months, and median follow-up time after starting therapy was 17.5 months.

Eleven percent of patients with preexisting AID developed grade 3 or 4 irAEs, which is similar to 7%-15% of patients in clinical trials. Although 23% of patients experienced a flare of their preexisting AID, these flares were generally mild – no patients discontinued immunotherapy because of a flare. In contrast, 14% of patients halted therapy because of toxicity, a marginally higher number than 3%-8% of patients in trials.

Checkpoint inhibitors are now a mainstay treatment for a lung cancer, including three approved drugs: nivolumab, pembrolizumab, and atezolizumab. “Almost every patient with advanced NSCLC will likely receive a [checkpoint] inhibitor at some point over the course of their disease,” the authors noted. As checkpoint inhibitors may lead to fatal irAEs, the possible interplay between these immunotherapies and AID requires investigation.

“Our study adds to the growing body of evidence supporting the use of immunotherapy in patients with cancer with preexisting AID, albeit with close monitoring for adverse events,” the researchers concluded.

SOURCE: Leonardi GC et al. J Clin Oncol. 2018* May 20. doi: 10.1200/JCO.2017.77.0305.

*Correction, 5/22/18: An earlier version of this article misstated the year in this citation.

For patients with non–small-cell lung cancer (NSCLC), preexisting autoimmune disease (AID) does not increase the risk of immune-related adverse events (irAEs) with checkpoint inhibitor therapy, according to investigators.

Flares of AID during therapy were generally mild, and toxicity rates were only slightly increased in patients with AID, they wrote in Journal of Clinical Oncology.

Approximately 14%-25% of patients with lung cancer also have AID, but patients with AID are typically excluded from clinical trials. “This presents a tremendous knowledge gap,” wrote lead author Giulia C. Leonardi, MD, of the Dana-Farber Cancer Institute in Boston, and coauthors.

The retrospective study comprised 56 patients with NSCLC and preexisting autoimmune disease from five academic cancer centers. Almost half of the patients had a rheumatologic disorder, 29% had a dermatologic disorder, 16% had an endocrine disorder, 11% had inflammatory bowel disease, 5% had a neurologic condition, 3% had rheumatic fever, and one patient (2%) had autoimmune hemolytic anemia.

Patients received either a programmed death-1 or programmed death-ligand 1 inhibitor as monotherapy. Median treatment time was 3.1 months, and median follow-up time after starting therapy was 17.5 months.

Eleven percent of patients with preexisting AID developed grade 3 or 4 irAEs, which is similar to 7%-15% of patients in clinical trials. Although 23% of patients experienced a flare of their preexisting AID, these flares were generally mild – no patients discontinued immunotherapy because of a flare. In contrast, 14% of patients halted therapy because of toxicity, a marginally higher number than 3%-8% of patients in trials.

Checkpoint inhibitors are now a mainstay treatment for a lung cancer, including three approved drugs: nivolumab, pembrolizumab, and atezolizumab. “Almost every patient with advanced NSCLC will likely receive a [checkpoint] inhibitor at some point over the course of their disease,” the authors noted. As checkpoint inhibitors may lead to fatal irAEs, the possible interplay between these immunotherapies and AID requires investigation.

“Our study adds to the growing body of evidence supporting the use of immunotherapy in patients with cancer with preexisting AID, albeit with close monitoring for adverse events,” the researchers concluded.

SOURCE: Leonardi GC et al. J Clin Oncol. 2018* May 20. doi: 10.1200/JCO.2017.77.0305.

*Correction, 5/22/18: An earlier version of this article misstated the year in this citation.